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J McEneny

Publications and source records attributed to J McEneny.

At least 19 recordsLinked to original sources
PubMed2003

Oxidative modification of triacylglycerol-rich lipoproteins.

Lipoprotein oxidation is thought to play a pivotal role in the evolution of atherosclerosis. Low-density lipoprotein (LDL) is the main source of oxidized lipid in the arterial wall. Oxidation of LDL alters its properties in a number of ways, making it more atherogenic, but oxidation of other lipoprotein classes may also be important. Common mechanisms are likely to contribute to the oxidation of all lipoprotein classes, with enzyme-mediated oxidation likely to be most important. Antioxidant content, fatty acid composition, particle size and the presence of seeding hydroperoxides also influence oxidative reactions. Larger triglyceride-rich lipoproteins are less likely to enter the arterial wall than LDL, but when oxidized will deliver a greater oxidant load to the arterial wall.

Animals↗
PubMed2002

Effects of GH on lipid peroxidation and neutrophil superoxide anion-generating capacity in hypopituitary adults with GH deficiency.

OBJECTIVES: Untreated growth hormone deficiency (GHD) is implicated in the increased cardiovascular risk associated with adult hypopituitarism. Oxidative stress, predisposing to lipid peroxidation, may be an important mediator of endothelial dysfunction, a pro-atherogenic state associated with adult GHD. DESIGN AND PATIENTS: In a randomized, double-blind, placebo-controlled study we investigated the effects of GH replacement on low-density lipoprotein (LDL) oxidation and neutrophil superoxide (O(-)(2)) generating capacity in 32 GHD adults (19 males, 13 females; age range 19-64 years) over 3 months. Thirty age- and sex-matched healthy controls were also studied. MEASUREMENTS: Lipid hydroperoxides (HPOs) in plasma were measured using the ferrous oxidation with xylenol orange (FOX) assay. The susceptibility of LDL to oxidation was assessed by the copper-catalysed lag phase of LDL oxidation. Neutrophil O(-)(2)- generating capacity was assessed by a lucigenin-based chemiluminescent assay of NADPH oxidase activity. Body composition was assessed using bioelectrical impedance analysis. RESULTS: Compared to controls, GHD subjects had higher LDL cholesterol (4.0 +/- 0.8 vs. 3.5 +/- 0.9 mmol/l, P < 0.01) and higher triglyceride concentrations (2.3 +/- 1.5 vs. 1.1 +/- 0.7 mmol/l, P < 0.001) but lower HDL cholesterol (1.1 +/- 0.3 mmol/l vs. 1.4 +/- 0.4 mmol/l, P < 0.01), lower levels of HPOs (0.72 +/- 0.35 vs. 0.92 +/- 0.20 microm, P < 0.01) and lower basal (2.5 +/- 1.5 vs. 4.5 +/- 2.3 mV/5 x 10(5) neutrophils, P < 0.01) and peak post-activation levels (23.2 +/- 11.1 vs. 34.4 +/- 15.6 mV/5 x 10(5) neutrophils, P < 0.01) of neutrophil O(-)(2)- generation. GH replacement resulted in an increase in HPOs from 0.70 +/- 0.39 to 0.86 +/- 0.19 microm (P < 0.05), although there was no change in the lag time of LDL oxidation. Neutrophil O(-)(2)- generating capacity was enhanced with a rise in basal O(-)(2)- generation from 2.8 +/- 1.4 to 5.4 +/- 4.6 mV/5 x 10(5) neutrophils (P < 0.05) and in peak post-activation O(-)(2)- generation from 21.9 +/- 9.5 to 35.8 +/- 21.7 mV/5 x 10(5) neutrophils (P < 0.05). LDL cholesterol was reduced from 4.1 +/- 0.8 mmol/l to 3.5 +/- 0.8 mmol/l (P < 0.01). No significant changes in measured parameters occurred in the placebo group. CONCLUSIONS: Adult GHD is associated with reduced lipid peroxidation and impaired neutrophil O(-)(2)- generating capacity, both of which are reversible with GH replacement. Our data suggest that: (i) that oxidative stress is not a major feature of the pro-atherogenic state in hypopituitary adults with GHD and (ii) a role for GH in modulating neutrophil function and leucocyte-lipoprotein interactions.

Adult↗
PubMed2001

Lipoprotein oxidation and atherosclerosis.

Lipoprotein oxidation is a key early stage in the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) is initiated by both enzyme-mediated and non-enzymic mechanisms in vivo, and oxidized LDL has many atherogenic properties. Oxidation of LDL in vivo is likely to be influenced by local environmental factors, such as pH. The composition of LDL is also important, including such factors as antioxidant content, fatty acid composition and particle size.

Arteriosclerosis↗
PubMed2000

Very low density lipoprotein subfractions in Type II diabetes mellitus: alterations in composition and susceptibility to oxidation.

AIMS/HYPOTHESIS: Type II (non-insulin-dependent) diabetes mellitus is associated with raised triglycerides and increased very low density lipoprotein cholesterol. The aim of this study was to assess if very low density lipoprotein subfraction composition and potential to oxidise were altered in this condition. METHODS: Very low density lipoprotein was separated into four subfractions (A-->D) by a novel, rapid ultracentrifugation procedure. Analysis of each subfraction included lipid and fatty acid composition. Preformed peroxides were measured spectrophotometrically and conjugated dienes were used as an indicator of in vitro lipid oxidation. RESULTS: In all results we compared patient and control subfractions. Mean fasting plasma glucose was 8.9 +/- 2.0 mmol/l in patients vs 5.1 +/- 0.4 mmol/l in control subjects (p < 0.001); patient HbA1c was 7.6 +/- 1.4%. Patient total lipid standardised for apo B was higher than controls in subfractions A, B and C; A, 201 vs 60; B, 191 vs 40; C, 63 vs 21; D, 29 vs 34 micromol lipid per mg apo B (p < 0.05). Preformed peroxides were higher in all patient subfractions compared with controls: A, 340 vs 48; B, 346 vs 42; C, 262 vs 28; D, 54 vs 16 nmol per mg apo B (p < 0.001). Patient subfractions A and D were more susceptible to in vitro oxidation. Monounsaturated fatty acids were lower in patients subfractions, 35.2 vs 36.7; B, 35.1 vs 38.7; C, 34.4 vs 36.5; D, 33.0 vs 35.5 as per cent total (p < 0.05). CONCLUSIONS/INTERPRETATION: These results indicate abnormalities in very low density lipoprotein subfraction composition and oxidation profile in Type II diabetic subjects, which are characteristic of more atherogenic particles and that may contribute to the development of cardiovascular disease in these patients.

Apolipoproteins B↗
PubMed2000

Reperfusion injury is greater with delayed restoration of venous outflow in concurrent arterial and venous limb injury.

BACKGROUND: Complex limb trauma often involves combined arterial and venous injury, and the resultant ischaemia-reperfusion injury (IRI) causes both local and remote organ injury. This study assessed the influence of the timing of restoration of venous drainage on IRI. METHODS: Male New Zealand white rabbits (n = 36) were randomized into six groups: sham operation (group 1) and unilateral hind limb arterial and venous occlusion for 1 h followed by no reflow for 2 h (group 2), arterial and venous reflow for 2 h (group 3), arterial reflow alone for 2 h (group 4), arterial reflow alone for 1 h followed by arterial and venous (delayed) reflow for a further 1 h (group 5), and pretreatment with an enteral combination antioxidant before occlusion of both artery and vein and delayed venous reflow (group 6). Plasma hydroperoxide (HPO) and glutathione peroxidase concentration, hind limb skeletal muscle and lung tissue wet : dry weight ratios and myeloperoxidase (MPO) concentration were measured. RESULTS: The plasma HPO level in the femoral vein effluent was significantly greater after delayed venous reflow (mean(s.e.m.) 2. 02(0.54) micromol/l) than in control animals (0.98(0.10) micromol/l) (P < 0.05). There was also a significantly greater tissue wet : dry weight ratio after delayed venous reflow than in controls, in skeletal muscle (mean(s.e.m.) 6.89(0.14) versus 5.34(0.54); P < 0. 05) and lung (9.20(1.14) versus 7.23(0.38); P < 0.05) tissue. Lung tissue MPO activity was significantly greater after delayed venous reflow compared with controls (3.20(0.28) versus 1.86(0.14) units/g; P < 0.005), and also in comparison to simultaneous arterial and venous reflow (2.40(0.24) units/g; P < 0.05). In the antioxidant pretreatment group there was no significant increase in plasma HPO concentration, tissue MPO level or tissue wet : dry weight ratio compared with the control group. CONCLUSION: In combined major arterial and venous injury of the limb, delayed restoration of venous drainage leads to significantly greater local skeletal muscle injury and remote neutrophil-mediated lung injury. These results support the clinical rationale for early restoration not only of arterial inflow but also venous drainage by means of intraluminal shunts.

Animals↗
PubMed1999

HDL composition and HDL antioxidant capacity in patients on regular haemodialysis.

Recent evidence suggests that HDL can directly inhibit LDL oxidation, a key early stage in atherogenesis. Patients with chronic renal failure are at increased cardiovascular risk, have reduced HDL levels and altered HDL composition. We have therefore investigated whether compositional changes in HDL lead to decreased HDL antioxidant capacity in these patients. In comparison to control subject HDL, patient HDL contained less total cholesterol, cholesterol esters, phospholipids and alpha-tocopherol. LDL, HDL and LDL + HDL were standardised for protein and oxidised in the presence of Cu2+. The rate of propagation during HDL oxidation was reduced in the patient group (3.28+/-0.65 x 10(-5) vs. 4.60+/-0.97 x 10(-5) abs. U/min, P < 0.01). Lipid peroxide generation in patient HDL was decreased: 6.56+4.4 versus 13.42+/-7.0 nmol malondialdehyde (MDA)/mg HDL protein after 90 min and 14.45+/-3.8 versus 20.11+/-7.8 nmol MDA/mg HDL protein after 180 min. This is attributable to reduced HDL polyunsaturated fatty acid content in patients (0.53+/-0.12 vs. 0.72+/-0.16 mmol/g HDL, P < 0.01). The inhibitory effect of HDL on LDL oxidation was similar: 71 and 33% for patient HDL compared to 68 and 31% for control HDL, after 90 and 180 min, respectively. Compositional changes of HDL in patients on haemodialysis did not affect the antioxidant capacity of HDL after standardisation for HDL protein. However, reduced HDL levels in vivo may result in reduced HDL antioxidant capacity in these patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1999

Absorption and antioxidant effects of quercetin from onions, in man.

OBJECTIVE: To investigate the in vivo effects of quercetin following the ingestion of fried onions. DESIGN: Five healthy volunteers, three males and two females aged between 25 and 39 y, ingested 225 g of fried onions after an overnight fast and peripheral venous blood was collected 0, 2, 4, 24 and 48 h after consumption. Quercetin in the plasma, total antioxidant capacity and susceptibility of low density lipoproteins (LDL) to oxidation were measured. RESULTS: Following the onion meal, quercetin levels increased from baseline values (28.4 +/- 1.9 ng/ml) to peak after 2 h (248.4 +/- 103.9 ng/ml), decreasing to baseline again after 24 h (P > 0.05). This was accompanied by an increase in the total antioxidant activity of the plasma from baseline (1.70 +/- 0.04 mmol/l trolox equivalents) to 1.75 +/- 0.10 mmol/l trolox equivalents after 2 h and 1.76 +/- 0.08 mmol/l trolox equivalents after 4 h. There was no significant change in the susceptibility of the plasma or the isolated LDL to oxidation over the 48 h period after consumption of the fried onions. In view of these negative findings, we isolated LDL and other lipoproteins from plasma at each time point. Quercetin was not detected in either LDL or VLDL, but was present in the HDL fraction, although this fraction also contains other proteins including albumin. CONCLUSIONS: Quercetin can be absorbed in humans from dietary sources to high enough concentrations to increase the overall antioxidant activity of the plasma. Quercetin, however, has a strong affinity for protein and provides no direct protective effect during LDL oxidation.

Adult↗
PubMed1998

Black tea consumption does not protect low density lipoprotein from oxidative modification.

OBJECTIVE: To investigate the in vivo and in vitro effects of black tea on the oxidative modification of low density lipoprotein (LDL). DESIGN: The antioxidant activity of the tea was studied in vitro by measuring the resistance of the LDL to oxidative modification in the presence of copper. The effects of tea consumption in vivo were investigated in two settings. Firstly, to assess the acute effects of tea consumption, five fasting healthy subjects ingested 600 mls (50.7+/-5.4 mg flavonoids) of black tea and peripheral venous blood was collected at 0, 30, 60, 90, 120 and 180 min after consumption. Secondly, to assess the effects of chronic tea consumption, a randomised crossover trial of tea (126.8+/-13.5 mg flavonoids) and coffee consumption was carried out in ten healthy subjects. RESULTS: Black tea extract increased the resistance of LDL in vitro in a concentration dependent manner. There was no significant change in total plasma antioxidant capacity or susceptibility of the LDL to oxidation over the 3 h period after consumption of black tea. The four-week crossover study in which coffee was used as a control against the black tea showed no significant difference in the total plasma antioxidant capacity or susceptibility of LDL to oxidation between the tea and coffee groups. Serum lipids, including total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol did not change significantly throughout the study. CONCLUSIONS: The consumption of moderate quantities of black tea acutely or for one week does not increase plasma total antioxidant capacity or alter the susceptibility of LDL to oxidation.

Adult↗
PubMed1998

A simple method for assessing copper-mediated oxidation of very-low-density lipoprotein isolated by rapid ultracentrifugation.

The association of very-low-density lipoprotein (VLDL) with atherosclerosis remains controversial. However, studies have shown that oxidative modification of VLDL can promote foam cell formation, leading to the development of atherosclerosis. A rapid method is described which will allow the significance of VLDL oxidation to be assessed in clinical studies. VLDL was isolated from heparinized plasma by a 1-h, single spin ultracentrifugation. Total protein was standardized to 25 mg/L. Oxidation was promoted by the addition of copper ions (17.5 mumol/L, final concentration) incubated at 37 degrees C. Conjugated diene production was followed at 234 nm. Total assay preparation time was 2 h. Urate greatly inhibited the oxidation of VLDL and was successfully removed by size exclusion chromatography. VLDL isolated from frozen plasma (-70 degrees C) was stable for 15 weeks. This simple, rapid method for the isolation of VLDL may be applied to assess the significance of VLDL oxidation in disease.

Copper↗
PubMed1997

Susceptibility of VLDL to oxidation in patients on regular haemodialysis.

Oxidation of VLDL in vitro increases macrophage uptake and promotes foam cell formation, and the dyslipidaemia of chronic renal failure is characterised by an increase in VLDL. However, little information is available with regard to the susceptibility of VLDL to oxidation in patients at increased risk of atherosclerosis. We have therefore assessed the composition and susceptibility to oxidation of VLDL from haemodialysis patients and control subjects. VLDL from haemodialysis patients contained increased lipid hydroperoxides (81.6 +/- 12.6 versus 16.1 +/- 3.4 nmol/mg protein, P < 0.001) and malondialdehyde (35.9 +/- 7.3 versus 16.0 +/- 4.1 nmol/mg protein, P < 0.05). Susceptibility to oxidation was increased as shown by an increased rate of propagation of the copper induced lipid peroxidation chain-reaction (11.6 +/- 1.5 x 10(-5) versus 7.6 +/- 1.1 x 10(-5)abs. U/min, P < 0.05) and a greater increase in conjugated diene formation during peroxidation (0.47 +/- 0.04 versus 0.25 +/- 0.03 abs. U, P < 0.001). Increased VLDL peroxidation in dialysis patients may contribute to the increased risk of cardiovascular disease observed in this group of patients.

Adult↗
PubMed1996

The effect of various oestrogens and progestogens on the susceptibility of low density lipoproteins to oxidation in vitro.

OBJECTIVE: To investigate the effect of different oestrogens and progestogens, at various concentrations, on the oxidation of low density lipoproteins (LDL) in vitro. METHODS: Oestradiol, oestrone, oestriol and equilin, as well as medroxyprogesterone acetate, norgestrel and norethisterone, were added to isolated male LDL, before it was oxidised in the presence of copper ions at 37 degrees C. The oxidation process was monitored spectrophotometrically by the production of conjugated dienes. The lag time to oxidation and the maximum rate of propagation of the reaction were used as measures of the resistance and susceptibility of the LDL to oxidation respectively. RESULTS: The lag time was increased from 43.7 +/- 1.5 min (mean +/- SEM) for LDL without any added hormone, to 81.2 +/- 1.0 min by 1 microM oestradiol (P < 0.01), 77.9 +/- 4.6 min by 1 microM oestrone (P < 0.01), 67.6 +/- 6.2 min by 1 microM equilin (P < 0.01), and 51.8 +/- 2.8 min by 1 microM oestriol (P < 0.05). The maximum rate of propagation of the reaction was decreased from 0.23 +/- 0.01 nmol conjugated dienes/mg LDL-protein/min (mean +/- SEM) (control LDL) to 0.14 +/- 0.006 nmol/mg/min by oestradiol (P < 0.01), 0.15 +/- 0.009nmol/mg/min by oestrone (P < 0.01), 0.17 +/- 0.012 nmol/mg/min by equilin (P < 0.01) and 0.19 +/- 0.014 nmol/mg/min (P < 0.05) by oestriol. The progestogens alone had no antioxidant effect, nor did their addition to the oestrogens influence their antioxidant activity. CONCLUSIONS: These results demonstrate that all oestrogens investigated have an inhibitory effect on LDL oxidation in vitro. The magnitude of this effect varied, being of the order oestradiol > oestrone > equilin > oestriol.

Dose-Response Relationship, Drug↗
PubMed1995

Carbamylation inhibits the ferroxidase activity of caeruloplasmin.

The ferroxidase activity of caeruloplasmin (EC 1.16.3.1) is an important antioxidant defence mechanism in man. In chronic renal failure proteins become carbamylated as a result of reactions with urea-derived cyanate. We have therefore investigated the effects of carbamylation on the ferroxidase activity of caeruloplasmin. Increasing degrees of carbamylation produce a progressive impairment of ferroxidase activity measured using o-dianisidine as substrate, and the ability of caeruloplasmin to load ferrous iron onto ovotransferrin is reduced. Carbamylation of caeruloplasmin may contribute to reduced antioxidant capacity in patients with renal failure.

Ceruloplasmin↗
PubMed1995

A rapid method for measurement of the susceptibility to oxidation of low-density lipoprotein.

Oxidation of low-density lipoprotein (LDL) may be important in the pathogenesis of atherosclerosis. We describe a method which measures the oxidation resistance of LDL isolated by a rapid procedure without added antioxidants. LDL was isolated from heparinized plasma by density gradient ultracentrifugation and desalted by gel filtration. The protein concentration was standardized to 50 mg/L and oxidation was promoted by copper (2 mumol/L) at 37 degrees C. The total sample preparation time was 2.5 h. Conjugated diene production was monitored at lambda = 234 nm with computation of the lag time. LDL oxidation was inhibited by EDTA but not heparin. Albumin inhibited LDL oxidation but only in concentrations greater than 50 mg/L. LDL was stable in frozen plasma (-70 degrees C) for 10 weeks, but unstable in the isolated and desalted state. The lag time for LDL from patients treated with the antioxidant probucol was markedly prolonged compared to normal subjects.

Albumins↗
PubMed1994

Oxidation of low density lipoprotein in patients on regular haemodialysis.

Patients undergoing chronic haemodialysis are known to have a high incidence of premature atherosclerosis for reasons which have not been fully elucidated. The susceptibility of low density lipoprotein (LDL) to oxidation by copper ions in vitro is widely used as a measure of its atherogenicity in vivo. We measured the susceptibility of LDL to oxidation using copper ions in haemodialysis patients and found, surprisingly, a markedly increased resistance to oxidation. The experiment was therefore repeated using an alternative free radical generator, AAPH [2,2'-azobis-(2-amidinopropane hydrochloride)], to promote LDL oxidation; using AAPH, the susceptibility to oxidation was similar in the dialysis group compared to controls. Abnormal LDL composition in the dialysis patients was also demonstrated. We suggest that, in such situations, susceptibility of LDL to oxidation in vitro may be highly dependent on the biochemical method employed and therefore may not accurately reflect atherogenic risk.

Amidines↗
PubMed1994

The effect of probucol and vitamin E treatment on the oxidation of low-density lipoprotein and forearm vascular responses in humans.

This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double-blind parallel group study, 24 hypercholesterolaemic patients already on treatment with simvastatin (20 mg day-1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG-monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo.

Adult↗
PubMed1993

Rare apolipoprotein E variant identified in a patient with type III hyperlipidaemia.

We report a rare apolipoprotein E variant in an Irish female with Type III hyperlipidaemia who has the phenotype E2E1 as determined by isoelectric focusing. Sequence analysis of the apolipoprotein E gene from the proband and from four other family members, using DNA amplified by the polymerase chain reaction, demonstrated the presence of a point mutation in the common epsilon 2 allele with a G-->A transition at nucleotide 3791. This was confirmed by digestion with the restriction endonuclease TaqI, which cuts at a new site within the apolipoprotein E gene, created by the base change. This mutation results in a substitution of aspartic acid for glycine at position 127 of the mature protein. We believe this to be the first description of this apolipoprotein E variant in a family from the British Isles. The mutation appears to be 'recessive' with respect to the expression of Type III hyperlipidaemia, although it may be somewhat more potent in this regard than the parent epsilon 2 allele. The Type III hyperlipidaemia is responsive to treatment with diet and gemfibrozil.

Adult↗